[Federal Register Volume 82, Number 12 (Thursday, January 19, 2017)]
[Rules and Regulations]
[Pages 6197-6210]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-00857]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF AGRICULTURE
Animal and Plant Health Inspection Service
7 CFR Part 331
9 CFR Part 121
[Docket No. APHIS-2014-0095]
RIN 0579-AE08
Agricultural Bioterrorism Protection Act of 2002; Biennial Review
and Republication of the Select Agent and Toxin List; Amendments to the
Select Agent and Toxin Regulations
AGENCY: Animal and Plant Health Inspection Service, USDA.
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: In accordance with the Agricultural Bioterrorism Protection
Act of 2002, we are amending and republishing the list of select agents
and toxins that have the potential to pose a severe threat to animal or
plant health, or to animal or plant products. The Act
[[Page 6198]]
requires the biennial review and republication of the list of select
agents and toxins and the revision of the list as necessary. This
action will amend the regulations in several ways, including the
addition of provisions to address the inactivation of select agents,
provisions addressing biocontainment and biosafety, and clarification
of regulatory language concerning security, training, incident
response, and records. These changes will increase the usability of the
select agent regulations as well as providing for enhanced program
oversight. After carefully considering the technical input of subject
matter experts and recommendations from Federal advisory groups, we
have decided not to finalize the proposed changes to the contents of
the list of select agents and toxins at this time. In a companion
document published in this issue of the Federal Register, the Centers
for Disease Control and Prevention has made parallel regulatory
changes.
DATES: Effective February 21, 2017.
FOR FURTHER INFORMATION CONTACT: Dr. Freeda Isaac, National Director,
Agriculture Select Agent Services, APHIS, 4700 River Road, Unit 2,
Riverdale, MD 20737-1231; (301) 851-3300, Option 3.
SUPPLEMENTARY INFORMATION:
Background
The Public Health Security and Bioterrorism Preparedness and
Response Act of 2002 (referred to below as the Bioterrorism Response
Act) provides for the regulation of certain biological agents that have
the potential to pose a severe threat to both human and animal health,
to animal health, to plant health, or to animal plant health, or to
animal and plant products. The Animal and Plant Health Inspection
Service (APHIS) has the primary responsibility for implementing the
provisions of the Act within the United States Department of
Agriculture (USDA). Veterinary Services (VS) select agents and toxins
are those that have been determined to have the potential to pose a
severe threat to animal health or animal products. Plant Protection and
Quarantine (PPQ) select agents and toxins are those that have the
potential to pose a severe threat to plant health or plant products.
Overlap select agents and toxins are those that have been determined to
pose a severe threat to both human and animal health or to human health
and animal products. Overlap select agents are subject to regulation by
both APHIS and the Centers for Disease Control and Prevention (CDC),
which has the primary responsibility for implementing the provisions of
the Bioterrorism Response Act for the Department of Health and Human
Services (HHS).
Subtitle B (which is cited as the ``Agricultural Bioterrorism
Protection Act of 2002'' and referred to below as the Act), section
212(a), provides, in part, that the Secretary of Agriculture (the
Secretary) must establish by regulation a list of each biological agent
and each toxin that the Secretary determines has the potential to pose
a severe threat to animal or plant health, or to animal or plant
products. Paragraph (a)(2) of section 212 requires the Secretary to
review and republish the list every 2 years and to revise the list as
necessary. In this document, we are amending and republishing the list
of select agents and toxins based on the findings of our fourth
biennial review of the list.
In determining whether to include an agent or toxin on the list,
the Act requires that the following criteria be considered:
The effect of exposure to the agent or the toxin on animal
and plant health, and on the production and marketability of animal or
plant products;
The pathogenicity of the agent or the toxin and the
methods by which the agent or toxin is transferred to animals or
plants;
The availability and effectiveness of pharmacotherapies
and prophylaxis to treat and prevent any illness caused by the agent or
toxin; and
Any other criteria that the Secretary considers
appropriate to protect animal or plant health, or animal or plant
products.
We use the term ``select agents and toxins'' throughout the
preamble of this rule. Unless otherwise specified, the term ``select
agents and toxins'' will refer to all agents or toxins listed by APHIS.
When it is necessary to specify the type of select agent or toxin, we
will use the following terms: ``PPQ select agents and toxins'' (for the
plant agents and toxins listed in 7 CFR 331.3), ``VS select agents and
toxins'' (for the animal agents and toxins listed in 9 CFR 121.3), or
``overlap select agents and toxins'' (for the overlap agents and toxins
listed in both 9 CFR 121.4 and 42 CFR 73.4).
On January 19, 2016, we published in the Federal Register (81 FR
2762-2774, Docket No. APHIS-2014-0095) a proposal \1\ to amend and
republish the list of select agents and toxins that have the potential
to pose a severe threat to animal or plant health, or to animal or
plant products, and amend the regulations in order to add definitions
and clarify language concerning security, training, biosafety,
biocontainment, and incident response.
---------------------------------------------------------------------------
\1\ To view the proposed rule and the comments we received, go
to http://www.regulations.gov/#!docketDetail;D=APHIS-2014-0095.
---------------------------------------------------------------------------
We solicited comments concerning our proposal for 60 days ending
March 21, 2016. We received 24 comments by that date. They were from
researchers, scientific organizations, industry groups, laboratories,
and universities. Eighteen were supportive of the proposed action. The
remaining six comments are discussed below by topic.
Removal of Select Agents and Toxins
We proposed to amend the list of PPQ select agents and toxins
listed in 7 CFR 331.3 by removing three PPQ select agents and toxins
from the list: Peronosclerospora philippinensis (Peronosclerospora
sacchari), Sclerophthora rayssiae, and Phoma glycinicola (formerly
Pyrenochaeta glycines).
We also proposed to remove three overlap select agents and toxins
from the list set out in 9 CFR 121.4(b): Bacillus anthracis (Pasteur
strain), Brucella abortus and Brucella suis.
After carefully considering the technical input of subject matter
experts and recommendations from Federal advisory groups, we have
decided not to finalize the proposed changes to the list of select
agents and toxins at this time.
Definitions
In 7 CFR 331.1 and 9 CFR 121.1, we proposed to add definitions for
inactivation and kill curve to clarify terms contained within the
proposed inactivation provisions. As detailed later in this final rule,
we have removed the requirement for generation of a kill curve. We are
therefore not including the definition in the regulations.
One commenter suggested that we specify that a ``validated method''
was used for inactivation. The commenter said that the addition of the
word ``validated'' would ensure that tested and appropriate methods of
inactivation would be utilized.
We are eliminating the definition for inactivation and instead
adding a definition of validated inactivation procedure to the
regulations. This definition encompasses the prior definition of
inactivation as well as providing further detail which we believe will
be useful for regulated entities. Validated inactivation procedure is
defined as a procedure, whose efficacy is confirmed by data generated
from a viability testing protocol, to render a select agent non-viable
but allows the select agent to retain characteristics of interest for
[[Page 6199]]
future use; or to render any nucleic acids that can produce infectious
forms of any select agent virus non-infectious for future use. While
the commenter suggested we use the term ``method,'' we have decided to
use the term ``procedure'' in response to comments received on the CDC
docket.
The same commenter suggested that we add definitions of validated
sterility test and safety margin as these terms were both proposed for
use in the biocontainment and biosafety sections and could prove
confusing or be subject to misinterpretation.
Given that we are adding a definition of validated inactivation
procedure as described previously, we are not adding a definition of
validated sterility test. We are not adding a definition of safety
margin since that term will not be in the regulations.
While we did not receive any further comments regarding
definitions, in response to comments received by CDC and in the
interests of maintaining parity between the APHIS and CDC regulations,
we are adding a definition for viability testing protocol. That term,
which is now used in Sec. Sec. 331.3, 121.3, and 121.4, is defined as,
``a protocol to confirm the validated inactivation procedure by
demonstrating the inability of a select agent to replicate.''
Exclusions and Inactivation
We proposed to amend 7 CFR 331.3(d)(2), 9 CFR 121.3(d)(2), and 9
CFR 121.4(d)(2), which exclude nonviable select agents or nonfunctional
toxins from the requirements of the regulations, in order to clarify
our policy that an entity must use a validated procedure to render a
select agent nonviable or regulated nucleic acids non-infectious for
future use. This means that the method must be scientifically sound and
that it will produce consistent results each time it is used.
One commenter stated that we need to consistently address toxins
throughout the regulations and suggested adding language specifying
that required methods would also render a select toxin as
nonfunctional.
We did not include language concerning toxins because, unlike
select agents, toxins do not replicate. An inactivation failure with a
toxin therefore represents a lower level of risk and thus does not
justify the potential additional recordkeeping and reporting burden for
registered entities at this time. We may revisit this issue in the
future.
We proposed that inactivation include the use of one of the
following: The exact conditions of a commonly accepted method that has
been validated as applied (e.g., autoclaving), a published method with
adherence to the exact published conditions (i.e., extrapolations or
deductions are to be avoided), or in-house methods, only if validation
testing includes the specific conditions used and appropriate controls.
The same commenter also suggested that we require that the
inactivation process be repeatable.
We agree with the commenter that the inactivation process has to be
validated so that the results are repeatable. The definition of
validated inactivation procedure states that the procedure must be
supported by data generated from viability testing. A process that is
not repeatable would never be validated.
We also proposed that the entity develop a site-specific kill curve
in order to define the conditions of inactivation for each select agent
or regulated nucleic acid. If there are strain-to-strain variations in
the resistance of a select agent to the inactivation procedure, then a
specific kill curve would have to be developed for each strain that
undergoes the inactivation procedure. A new kill curve would have to be
created upon any change in procedure or inactivation equipment. In
addition, a validated sterility testing protocol would have to be
conducted in order to ensure that the inactivation method has rendered
a select agent nonviable or regulated nucleic acids non-infectious.
Several commenters raised objections regarding development and use
of the kill curve. We have considered these comments and determined
that the kill curve and safety margin requirements are not applicable
to all inactivation procedures and should therefore not be included in
the regulations. We are instead requiring that registered entities
develop a validated inactivation procedure by establishing parameters
for quantities of starting material and measures of uncertainty for
repeated successful inactivation. This is a broad performance standard
that will allow for flexibility given the variety of select agents and
toxins under regulation.\2\ In addition, for the sake of clarity and
efficiency, we have removed the requirements specific to extracts of
select agents, instead including them within the overall performance
standard for select agents and toxins as a whole.
---------------------------------------------------------------------------
\2\ Additional guidance regarding this performance standard has
been developed and is available on the Internet at
www.selectagents.gov.
---------------------------------------------------------------------------
One commenter said that, without more specific direction, the
subjectivity of individual inspectors would be the principal factor in
determining acceptable inactivation verification.
We will not review or approve inactivation protocols. We believe
this activity should be approved at the entity, which will allow for
researchers to continue to develop new inactivation procedures.
However, inspectors will verify that the entity has developed a
validated inactivation procedure and will review viability testing
results during the entity's inspection.
Another commenter asked that we provide minimum requirements for
the sterility testing protocol and specify whether or not this must be
site-specific or if validated methods of sterility testing given in
published journal articles may be followed.
We recognize that the limits of detection of the viability testing
procedures and expected variation from run to run, even when following
an inactivation procedure precisely precludes demonstrating full
sterility of an inactivated sample. These sources of error must be
considered when the entity establishes performance parameters for
inactivation procedures. While complete sterility is not a feasible
goal for material that is intended for further use, we expect that the
risk of live agent in materials that are removed from containment and
are thus no longer subject to select agent requirements will be as low
as realistically possible from both a safety and security perspective.
We will be addressing the need for onsite validation of both
inactivation protocols and viability testing in guidance.
The same commenter cited the guidance document entitled ``Non-
viable Select Agents and Nonfunctional Select Toxins and Rendering
Samples Free of Select Agents and Toxins,'' \3\ which states that,
``this guidance does not apply to inactivation for waste disposal.''
The commenter urged us to clearly and accurately describe what is
intended regarding verification of non-viability in the regulations,
stating that they had received comments from some inspectors indicating
confusion between inactivation validation requirements for moving
materials to a lower containment level and inactivation validation
requirements for waste disposal.
---------------------------------------------------------------------------
\3\ You may view this guidance document on the Internet at
http://www.selectagents.gov/guidance-nonviable.html.
---------------------------------------------------------------------------
We have modified the reporting requirements to require the
responsible official to investigate any viability of material that was
subjected to a validated inactivation protocol to
[[Page 6200]]
determine the reason of the inactivation failure. If the responsible
official is unable to determine the reason for this failure, he or she
must report the inactivation failure to CDC or APHIS. Our intention is
to require registered entities to create an environment where
inactivation failures are investigated to determine the root source of
the errors instead of re-subjecting the material to an inactivation
method that may be flawed or faulty. The revised language only requires
reporting of inactivation failures to CDC or APHIS when the responsible
official cannot determine the reason for the inactivation failure. We
are also clarifying that these provisions apply only to those select
agents inactivated for future use as non-select agents and not those
intended for waste disposal.
Two commenters asked about the minimum percentage of samples
required to be tested to constitute a ``representative sample.''
Another commenter suggested that inactivated lots be stored with
documentation that demonstrates that the lot has met the established
standard, but added that it is impractical to conduct validated
sterility testing on every sample that is inactivated. The commenter
claimed that implementing such a requirement would waste specimens
where limited volumes are available, be costly in terms of technical
time and resources, and is scientifically unjustified.
Successful implementation of the required validated inactivation
procedure and the subsequent data derived from viability testing using
that procedure will determine the extent of sampling required. We have
removed the sterility testing requirement to allow entities flexibility
in establishing and utilizing individualized, validated inactivation
procedures.
We also proposed to require that an entity conduct an annual review
of their site-specific standard operating procedures to ensure that
select agents or regulated nucleic acids that can produce infectious
forms of any select agent virus are inactivated by a safety margin and
revise as necessary.
Two commenters questioned our use of the term ``safety margin.''
The commenters requested that we remove or define the term, as its
meaning is unclear. The commenters further stated that the need for
including a safety margin is unclear and appears superfluous if the
intent of the requirement is to define the conditions that achieve
conditions that render 100 percent of the select agent non-viable or
noninfectious.
We are not defining ``safety margin'' as the proposed regulatory
text using this term will not be incorporated into the final rule.
Finally, we proposed that written records be kept for any select
agent that has been rendered nonviable or regulated nucleic acids that
have been rendered non-infectious.
Two commenters asked for clarification of the actions constituting
review, including description of any documentation that will be
expected to demonstrate compliance with the requirement. The commenters
wanted to know if it was our expectation that the kill curve and
sterility testing be repeated and verified annually, or if this is a
review of data and written procedures.
In response, we have modified the language regarding review of
site-specific standard operating inactivation procedures to clarify
that the entity should review these procedures to determine if they are
being adhered to by staff. The annual review requirement does not
necessarily involve revalidating inactivation procedures. This review
may simply take the form of an evaluation of the site-specific standard
operating inactivation procedures to ensure the inactivation conditions
used and upper agent limits found in validation data are consistent and
that the entity staff are following the site-specific standard
operating inactivation procedures. At times an entity may need to
revalidate inactivation procedures during the annual review. For
example, review may be needed if the entity finds that staff are not
adhering to standard operating procedures or if the entity wants to
deviate from the established, validated inactivation procedure.
While we did not receive any further comments on this issue, in
response to comments received by CDC and in the interests of
maintaining parity between the APHIS and CDC regulations, we have made
the following changes:
Establishing that surrogate strains that are known to
possess properties equivalent to select agents may be used to validate
the required inactivation procedures under certain conditions;
Replacing the term ``extract'' with ``material containing
a select agent'' to clarify that the inactivation requirements apply to
such materials as serums or liquid cultures from which select agents
are typically removed via filtration without first undergoing
inactivation. This is intended to more accurately describe an element
of a two-step process: An inactivation step to destroy the select agent
and a second step intended to remove any remaining, viable select
agent; and
Clarification of when an entity may submit a waiver
request to the Administrator as well as the procedure for such
determinations.
Finally, in 7 CFR 331.3(d)(2), 9 CFR 121.3(d)(2), and 9 CFR
121.4(d)(2), we are replacing the term ``nonfunctional toxin'' with
``nontoxic toxin.'' We have determined that the term ``nonfunctional''
is overbroad and has caused confusion. Our intent was to exclude toxins
that can no longer exert their toxic effect and cause disease. For
example, Botulinum neurotoxin has three functional domains: Binding
domain, translocation domain, and catalytic domain. Each functional
domain may be solely manipulated such that the toxin is no longer toxic
and does not cause disease even though the other two domains may remain
functional. Note that the example provided is for a CDC toxin due to
the fact that APHIS does not currently regulate any select toxins.
Exemptions for Select Agents and Toxins
The provisions of 7 CFR 331.5, 9 CFR 121.5, and 9 CFR 121.6 concern
conditions under which entities may be exempted from the requirements
of the regulations. We proposed to add language to paragraph (a) in 7
CFR 331.5, 9 CFR 121.5, and 9 CFR 121.6 that specifies that entities
may be required to report identification of agents or toxins to other
appropriate authorities when required by Federal, State, or local law.
Specifically, we proposed to add provisions that state that we do not
regulate material containing select agents or toxins when it is in a
patient care setting and is not being collected or otherwise tested or
retained, nor do we regulate waste generated during delivery of patient
care. However, once delivery of patient care for the select agent or
toxin infection has concluded, waste would become subject to the
requirements of the regulations. If an entity cannot meet these
requirements, then the material may be transferred to another entity
according to the select agent regulations or destroyed using an
approved method. The decision to retain, transfer, or destroy any
specimens must be made within 7 calendar days of the conclusion of
patient care.
One commenter disagreed with adding such a provision to 9 CFR
121.5. The commenter said that VS should have authority to regulate
waste and carcasses from animals (i.e., veterinary patients) naturally
infected with select agents to ensure that infection does not spread to
other livestock or poultry. The commenter asked that we alter the
[[Page 6201]]
wording of the proposed section in order to specify that the
requirement refers to human patients only.
The provisions the commenter refers to relate to the care of human
patients only. However, it should be noted that any waste or carcasses
from animals infected with a select agent, provided the select agent or
toxin has not been intentionally introduced, cultivated, collected, or
otherwise extracted from its natural source, are already listed as
excluded in Sec. Sec. 121.3(d)(1) and 121.4(d)(1) of the regulations.
While we did not receive any further comments on this issue, in
response to comments received by CDC and in the interests of
maintaining parity between the APHIS and CDC regulations, we are
amending the text to clarify the following:
That patient care refers to actions by health care
professionals;
To clarify that destruction and transfer requirements
apply solely to waste generated in the course of patient care and not
specimens or samples taken from the patient; and
That specimens taken from a patient are not subject to the
regulations during the period in which they are directly associated
with the diagnosis, but all specimens taken and kept more than 7 days
after the conclusion of patient care are subject to the regulations.
Security, Biocontainment/Biosafety, and Incident Response Plans
The regulations require registered entities to develop and
implement a number of plans in order to ensure the safety and security
of the select agents they handle. These are:
A security plan, as described by the regulations in 7 CFR
331.11 and 9 CFR 121.11, that provides for measures sufficient to
safeguard the select agent or toxin against unauthorized access, theft,
loss, or release;
A biocontainment plan, in the case of PPQ select agents,
or a biosafety plan, in the case of VS and overlap select agents, as
described in the regulations in 7 CFR 331.12 and 9 CFR 121.12, that
provides for measures sufficient to contain the select agent or toxin
(e.g., physical structure and features of the entity, and operational
and procedural safeguards); and
An incident response plan, as described in the regulations
in 7 CFR 331.14 and 9 CFR 121.14, that provides for measures that the
registered entity will implement in the event of theft, loss, or
release of a select agent or toxin; inventory discrepancies; security
breaches (including information systems); severe weather and other
natural disasters; workplace violence; bomb threats and suspicious
packages; and emergencies such as fire, gas leak, explosion, power
outage, etc. The response procedures must account for hazards
associated with the select agent or toxin and appropriate actions to
contain such agent or toxin.
All of these plans require annual review and revision as necessary.
Drills or exercises must also be conducted at least annually to test
and evaluate the effectiveness of the plans. The plans must be reviewed
and revised, as necessary, after any drill or exercise and after any
incident. We proposed to require that these drills or exercises be
documented to include how the drill or exercise tested and evaluated
the plan, any problems identified, any corrective action taken, and the
names of the individuals who participated in the drill or exercise.
This will provide a more thorough accounting of required activities as
well as increasing the efficacy of the plans via testing and entity-
directed improvements. We proposed to add these requirements to 7 CFR
331.11(h), 331.12(e), 331.14(f), 9 CFR 121.11(h), 121.12(e), and
121.14(f).
One commenter stated that the requirement to record the names of
the individuals who participated in a given drill or exercise should be
limited to registered entity personnel and not include first responders
or others who participate. The commenter suggested that a list of the
participating external agencies (e.g., emergency management, emergency
medical services, fire department, etc.) could be included.
We agree with the commenter's suggestion and have updated the
regulations in order to clarify that only the names of individuals at
the registered entity are required to be listed. The entity may choose
to list the names of external agencies (e.g., fire department, police
department, etc.) that participated in the drill or exercise.
Comments on more specific proposed changes to these plans may be
found below.
Biocontainment/Biosafety Plan
Paragraph (a) of 7 CFR 331.12 and 9 CFR 121.12 requires that the
biocontainment or biosafety plan contain sufficient information and
documentation to describe the biosafety and containment procedures for
each select agent or toxin that the registered entity will possess. The
plan must also include a description of the biosafety and containment
procedures for any animals (including arthropods) or plants
intentionally or accidentally exposed to or infected with a select
agent. We proposed to additionally require that laboratory-specific
biocontainment and/or biosafety manuals must be accessible to
individuals working in those laboratories. This change will help to
foster an enhanced culture of responsibility by ensuring that
appropriate biocontainment and/or biosafety resources are available to
all staff with access to select agents and toxins within a select agent
laboratory.
One commenter suggested that the specific practice of making
manuals accessible is already employed by registered entities. The
commenter therefore questioned the need for a separate requirement.
We agree with the commenter and have removed the requirement.
Two commenters urged that, ``a description of the biosafety and
containment procedures for any animals (including arthropods) or plants
intentionally or accidentally exposed to or infected with a select
agent'' should clearly refer not only to animals within the laboratory
but also wildlife, domestic, and stray animals outside of the buildings
if they are potentially exposed via accidental release. The commenter
added that there should be a system in place to detect such incidents
if they occur.
The term ``any animals'' includes both laboratory animals as well
as the wild, domestic, and stray animals described by the commenters.
We will, however, add specific clarification to the guidance documents
associated with the biocontainment and biosafety plans.
One commenter requested clarification regarding the term
``laboratory.'' The commenter wanted to know whether the term refers to
a single room, a building, or to a group of rooms (e.g., laboratory,
animal room, and necropsy) used by a principal investigator for a
research project. The commenter also requested clarification regarding
the phrase, ``must be available to each individual working in the
laboratory,'' asking if this would require creation of a specific
biocontainment or biosafety manual for each room.
We have clarified the language to state that ``biosafety and
containment procedures specific to use of the select agent or toxin by
the principal investigator must be available to each individual
involved with that project.'' This more appropriately ties the creation
and distribution of biocontainment and biosafety manuals to specific
projects, select agents, and people.
We also proposed to add specific provisions to the biocontainment
and biosafety plans that would require completion of a written risk
assessment for each procedure.
[[Page 6202]]
Two commenters stated that these requirements are unnecessary and
would prove excessively burdensome to researchers and the responsible
official and should be removed. The commenters said that the new
requirements regarding validation of inactivation procedures would
serve the same security function. The commenters added that APHIS
already has opportunity to review and require amendment of an entity's
biocontainment or biosafety plan as a condition of registration or as a
result of inspection.
We agree with the commenter that this level of detail would prove
unnecessarily burdensome. We have instead added language to 7 CFR
331.12(a)(1) and 9 CFR 331.12(a)(1) to explicitly require that the
biocontainment and biosafety plans include a description of the
hazardous characteristics of each agent or toxin listed on the entity's
registration and the biosecurity or biosafety risk associated with
laboratory procedures related to the select agent or toxin.
One commenter asked that we define ``risk assessment,'' given that
it is a very broad term and therefore open to interpretation. This
commenter and another requested that we provide basic templates for
these new required sections and indicate where registered entities and
entities seeking registration may find these templates.
We have revised and condensed the proposed language as a result of
this and other comments. It no longer includes the term ``risk
assessment.''
Training
We proposed to amend the regulations in 7 CFR 331.15 and 9 CFR
121.15, which concern provision of mandatory training for staff and
visitors who work in or visit areas where select agents or toxins are
handled or stored. We proposed to require that all individuals who have
received approval to have access to select agents and toxins must
undergo training regardless of whether they have access to those select
agents or toxins. The training would have to be completed within a year
of that individual's approval or prior to entry into an area where
select agents and toxins are used or stored, whichever occurs first.
Two commenters objected to the proposed addition, stating that we
should include a description of the level of training necessary for
personnel in varying positions with highly disparate job duties and
responsibilities. The commenters requested that we clarify that
required training will be conducted at a level appropriate to the
registered person's role and level of access to select agents.
We agree with the commenters' point and have altered the required
training language to clearly delineate the types of training required
for individuals with varying access levels.
One commenter asked that we clearly specify the requirements for
both initial and annual training. The commenter also asked that we
consider making training a prerequisite for access to select agents and
toxins.
While we made no changes to our regulatory language based on this
comment, the document entitled, ``Guidance for Meeting the Training
Requirements of the Select Agent Regulations'' \4\ will be updated to
provide further detail and assistance regarding the content of initial
and annual training. The regulations in 7 CFR 331.15(a)(1) and 9 CFR
121.15(a)(1) already require that each approved individual receive
information and training on biosecurity/biosafety, security (including
security awareness), and incident response before that individual has
access to any select agents and toxins.
---------------------------------------------------------------------------
\4\ You may view this document on the Internet at http://www.selectagents.gov/guidance-training.html.
---------------------------------------------------------------------------
Records
The regulations in 7 CFR 331.17 and 9 CFR 121.17 concern required
recordkeeping procedures for regulated entities as those records relate
to select agents and toxins. Paragraph (a)(3)(x) requires that
registered entities record the destruction of any toxins by
specifically noting the quantity of toxin destroyed, the date of such
action, and by whom. However, there is not an equivalent requirement
regarding the destruction of select agents. We proposed to add this
requirement in order to ensure consistency with the toxin provisions
and ensure proper tracking of select agents from acquisition to
destruction.
While we did not receive any comments on this issue, in response to
comments received by CDC and in the interests of maintaining parity
between the APHIS and CDC regulations, we are amending the text to
stipulate that registered entities must maintain a record of the select
agent used, purpose of use, and, when applicable, final disposition
(including destruction) for each select agent held in long-term
storage.
We also proposed to state that any records created that contain
information related to an entity's registration or its select agents
and toxins must be provided promptly upon request. We proposed to
specify that such records may include, but are not limited to,
biocontainment certifications, laboratory notebooks, institutional
biosafety and/or animal use committee minutes and approved protocols,
and records associated with occupational health and suitability
programs.
One commenter expressed concern regarding the requirement to keep
laboratory notebooks for inspection purposes. The commenter stated that
items may include proprietary intellectual property and requested
clarification regarding the information needed from the notebooks. The
commenter asked that we amend the regulatory language in order to
protect intellectual property interests and specify if any information
would be required from laboratory notebooks apart from that collected
for inventory purposes.
We agree with the commenter and we have clarified that only
information related to the requirements of the regulations must be
produced upon request. Such information may be found in biocontainment
certifications, laboratory notebooks, institutional biosecurity/
biosafety and/or animal use committee minutes and approved protocols,
and records associated with occupational health and suitability
programs. Accordingly, we will only be reviewing relevant portions of
any laboratory notebooks or documents and only if they contain
information related to any requirements of the regulations.
To ensure the accuracy of handwritten records, we also proposed to
specify that such records must be legible.
Another commenter suggested that we require that records be written
in ink and not pencil and should be signed and dated when appropriate.
We acknowledge this suggestion as good practice. However, in the
interests of not being overly prescriptive, we are leaving the
interpretation of ``legible'' up to individual registered entities.
Records for Select Agents in Long-Term Storage
Paragraph (a)(1) in both 7 CFR 331.17 and 9 CFR 121.17 requires
entities to maintain an accurate, current inventory for each select
agent (including viral genetic elements, recombinant and/or synthetic
nucleic acids, and organisms containing recombinant and/or synthetic
nucleic acids) held in long-term storage. We continue to receive
comments critical of that portion of the regulations. Criticism is
typically focused on the belief that a container-based inventory
requirement is not a
[[Page 6203]]
useful mechanism to track inventory of biological agents, since small
amounts could be stolen without detection and used to grow larger
quantities.
However, the Public Health Security and Bioterrorism Preparedness
and Response Act of 2002 obliges APHIS and CDC to include a requirement
for ``the prompt notification of the Secretary, and appropriate
Federal, State, and local law enforcement agencies, of the theft or
loss of listed agents and toxins'' in the regulations. We therefore
solicited comment regarding what regulatory requirement or requirements
should be implemented such that a registered entity could quickly
determine whether a select agent had been lost or stolen from long-term
storage without that registered entity first having an accurate,
current inventory for each select agent held in long-term storage.
Additionally, we solicited ideas concerning ways in which the current
regulations could be amended to address the possibility of theft of a
select agent from a container held in long-term storage.
One commenter stated that, while they understand the need for such
inventory and notification requirements, an enormous amount of time and
effort is spent during inspections validating that inventories are
accurate. The commenter said that this has resulted in the loss of
valuable virus isolates due to unintentional thawing, failure of
ultralow temperature freezers due to repeated opening and the resulting
loss of ultralow temperature, and inefficient use of employee time. The
commenter said that measuring the volumes of stored vials of bacteria
and viruses in the manner that toxins or other non-replicative select
agents are inventoried is illogical. The commenter acknowledged that it
is important to indicate the nature of the pathogens stored and the
numbers of vials in freezer stocks, but even the most fastidious
recordkeeping could not demonstrate that vials of replicative organisms
had not been accessed. The commenter stated that current select agent
practices allow for these stocks to be maintained in tamper-evident
stocks (e.g., security ties on freezer boxes) so that vials are not
individually removed, thawed, and measured. The commenter concluded
that requiring the use of tools of this nature in the case of
replicative organisms is a logical step that would not eliminate the
need to inventory, but which also would not degrade samples and allow
for detection of samples that may have disappeared.
We appreciate this comment and will continue to consider how the
recognition of theft and loss might be addressed through alternative
approaches.
Miscellaneous Changes
We are also adding a definition of principal investigator to the
regulations in 7 CFR 331.1 and 9 CFR 121.1 as it is used but not
defined in the APHIS regulations. The addition also serves to maintain
parity with the CDC regulations. Our definition is identical to that
used by CDC.
Therefore, for the reasons given in the proposed rule and in this
document, we are adopting the proposed rule as a final rule with the
changes discussed in this document.
Executive Order 12866 and Regulatory Flexibility Act
This final rule has been determined to be significant for the
purposes of Executive Order 12866 and, therefore, has been reviewed by
the Office of Management and Budget.
In accordance with 5 U.S.C. 604, we have performed a final
regulatory flexibility analysis, which is summarized below, regarding
the economic effects of this rule on small entities. Copies of the full
analysis are available on the Regulations.gov Web site (see footnote 1
in this document for a link to Regulations.gov) or by contacting the
person listed under FOR FURTHER INFORMATION CONTACT.
Sections 201 and 212(a)(2) of the Act require a biennial review and
republication of the select agent and toxin list, with revisions as
appropriate in accordance with this law. This final rule will implement
the recommendations of the fourth biennial review of select agent
regulations and has finalized changes that will increase their
usability as well as provide for enhanced program oversight. These
amendments include new provisions regarding the inactivation of select
agents, specific biosafety and toxin requirements and clarification of
regulatory language concerning security, training, and records. The
final rule will require that entities develop a validated inactivation
procedure by establishing parameters for quantities of starting
material and measures of uncertainty for repeated successful
inactivation. This is a broad performance standard that will allow for
flexibility given the variety of select agents and toxins under
regulation to define conditions of inactivation for each select agent
or regulated infectious nucleic acid and maintain written records of
having done so. Costs of complying with this amendment are expected to
be modest.
Currently, there are 291 entities registered with APHIS and CDC. Of
these entities, there are 240 registered to possess Tier 1 select
agents and toxins, including 78 academic, 29 commercial, 80 State
government, 37 Federal government, and 16 private (non-profit)
institutions, most of which are considered to be small entities. Based
on current recordkeeping and reporting requirements, an additional 10
to 20 hours per year may be required for maintaining records associated
with select agents or material containing select agents or regulated
nucleic acids that can produce infectious forms of any select agent
virus that have been subjected to a validated inactivation procedure or
a procedure for removal of viable select agents. At an imputed cost of
$33.40 per hour (GS-12, step 2), this additional time requirement per
entity will cost between $334 and $668 per year, or in total for all
registered entities between $80,000 and $160,000. Assuming that costs
of the rule could be considered to be significant if they exceeded 1
percent of revenue earned by the affected entities, revenues would need
to average less than $33,400 to $66,800 for this to be the case. While
the vast majority of the entities in industries potentially affected by
this rule, other than post-secondary institutions, can be considered
small, average annual revenues are well above this range.
Due to the reasons summarized here and explained in the analysis
accompanying this rule, the Administrator certifies that this action
will not have a significant economic impact on a substantial number of
small entities.
Executive Order 12988
This final rule has been reviewed under Executive Order 12988,
Civil Justice Reform. This rule: (1) Preempts all State and local laws
and regulations that are inconsistent with this rule; (2) has no
retroactive effect; and (3) does not require administrative proceedings
before parties may file suit in court challenging this rule.
Executive Order 13175
This rule has been reviewed in accordance with the requirements of
Executive Order 13175, Consultation and Coordination with Indian Tribal
Governments. Executive Order 13175 requires Federal agencies to consult
and coordinate with tribes on a government-to-government basis on
policies that have tribal implications, including regulations,
legislative comments or proposed legislation, and other policy
statements or actions that have substantial direct effects on one or
more Indian tribes, on the relationship between the Federal Government
and
[[Page 6204]]
Indian tribes or on the distribution of power and responsibilities
between the Federal Government and Indian tribes.
The Animal and Plant Health Inspection Service has assessed the
impact of this rule on Indian tribes and determined that this rule does
not, to our knowledge, have tribal implications that require tribal
consultation under E.O. 13175. If a Tribe requests consultation, the
Animal and Plant Health Inspection Service will work with the Office of
Tribal Relations to ensure meaningful consultation is provided where
changes, additions and modifications identified herein are not
expressly mandated by Congress.
Paperwork Reduction Act
In accordance with section 3507(d) of the Paperwork Reduction Act
of 1995 (44 U.S.C. 3501 et seq.), the reporting, recordkeeping, and
third-party disclosure requirements included this rule are in the
process of being reinstated by the Office of Management and Budget
under 0579-0213.
E-Government Act Compliance
The Animal and Plant Health Inspection Service is committed to
compliance with the E-Government Act to promote the use of the Internet
and other information technologies, to provide increased opportunities
for citizen access to Government information and services, and for
other purposes. For information pertinent to E-Government Act
compliance related to this rule, please contact Ms. Kimberly Hardy,
APHIS' Information Collection Coordinator, at 301-851-2483.
List of Subjects
7 CFR Part 331
Agricultural research, Laboratories, Plant diseases and pests,
Reporting and recordkeeping requirements.
9 CFR Part 121
Agricultural research, Animal diseases, Laboratories, Medical
research, Reporting and recordkeeping requirements.
Accordingly, 7 CFR part 331 and 9 CFR part 121 are amended as
follows:
Title 7--Agriculture
PART 331--POSSESSION, USE, AND TRANSFER OF SELECT AGENTS AND TOXINS
0
1. The authority citation for part 331 continues to read as follows:
Authority: 7 U.S.C. 8401; 7 CFR 2.22, 2.80, and 371.3.
0
2. Section 331.1 is amended by adding, in alphabetical order,
definitions of principal investigator, validated inactivation
procedure, and viability testing protocol to read as follows:
Sec. 331.1 Definitions.
* * * * *
Principal investigator. The one individual who is designated by the
entity to direct a project or program and who is responsible to the
entity for the scientific and technical direction of that project or
program.
* * * * *
Validated inactivation procedure. A procedure, whose efficacy is
confirmed by data generated from a viability testing protocol, to
render a select agent non-viable but allows the select agent to retain
characteristics of interest for future use; or to render any nucleic
acids that can produce infectious forms of any select agent virus non-
infectious for future use.
* * * * *
Viability testing protocol. A protocol to confirm the validated
inactivation procedure by demonstrating the material is free of all
viable select agent.
0
3. Section 331.3 is amended as follows:
0
a. By revising paragraph (d)(2).
0
b. By redesignating paragraph (d)(3) as paragraph (d)(9)
0
c. By adding paragraphs (d)(3) through (8) and (e)(3).
The additions and revision read as follows:
Sec. 331.3 PPQ select agents and toxins.
* * * * *
(d) * * *
(2) Nonviable select agents or nontoxic toxins.
(3) A select agent or toxin that has been subjected to
decontamination or a destruction procedure when intended for waste
disposal.
(4) A select agent or regulated nucleic acids that can produce
infectious forms of any select agent virus that has been subjected to a
validated inactivation procedure that is confirmed through a viability
testing protocol. Surrogate strains that are known to possess
equivalent properties with respect to inactivation can be used to
validate an inactivation procedure; however, if there are known strain-
to-strain variations in the resistance of a select agent to an
inactivation procedure, then an inactivation procedure validated on a
lesser resistant strain must also be validated on the more resistant
strains.
(5) Material containing a select agent that is subjected to a
procedure that removes all viable select agent cells, spores, or virus
particles if the material is subjected to a viability testing protocol
to ensure that the removal method has rendered the material free of all
viable select agent.
(6) A select agent or regulated nucleic acids that can produce
infectious forms of any select agent virus not subjected to a validated
inactivation procedure or material containing a select agent not
subjected to a procedure that removes all viable select agent cells,
spores, or virus particles if the material is determined by the
Administrator to be effectively inactivated or effectively removed. To
apply for a determination an individual or entity must submit a written
request and supporting scientific information to APHIS. A written
decision granting or denying the request will be issued.
(7) A PPQ select toxin identified in an original food sample or
clinical sample.
(8) Waste generated during the delivery of patient care by health
care professionals from a patient diagnosed with an illness or
condition associated with a select agent, where that waste is
decontaminated or transferred for destruction by complying with State
and Federal regulations within 7 calendar days of the conclusion of
patient care.
* * * * *
(e) * * *
(3) An individual or entity may make a written request to the
Administrator for reconsideration of a decision denying an application
for the exclusion of an attenuated strain of a select agent or a select
toxin modified to be less potent or toxic. The written request for
reconsideration must state the facts and reasoning upon which the
individual or entity relies to show the decision was incorrect. The
Administrator will grant or deny the request for reconsideration as
promptly as circumstances allow and will state, in writing, the reasons
for the decision.
* * * * *
0
4. Section 331.5 is amended as follows:
0
a. By revising paragraph (a)(1).
0
b. In paragraph (a)(2), by removing ``; and'' and adding a period in
its place.
0
c. By revising paragraph (a)(3).
The revisions read as follows:
Sec. 331.5 Exemptions.
(a) * * *
(1) Unless directed otherwise by the Administrator, within 7
calendar days after identification of the select agent or toxin, the
select agent or toxin is transferred in accordance with Sec. 331.16 or
destroyed on-site by a recognized sterilization or inactivation
process.
* * * * *
[[Page 6205]]
(3) The identification of the agent or toxin is reported to APHIS
or CDC, the specimen provider, and to other appropriate authorities
when required by Federal, State, or local law by telephone, facsimile,
or email. This report must be followed by submission of APHIS/CDC Form
4 to APHIS or CDC within 7 calendar days after identification.
* * * * *
0
5. Section 331.7 is amended as follows:
0
a. By redesignating paragraphs (b) through (k) as paragraphs (c)
through (l), respectively.
0
b. By adding a new paragraph (b).
The addition reads as follows:
Sec. 331.7 Registration and related security risk assessments.
* * * * *
(b) As a condition of registration, each entity is required to be
in compliance with the requirements of this part for select agents and
toxins listed on the registration regardless of whether the entity is
in actual possession of the select agent or toxin. With regard to
toxins, the entity registered for possession, use, or transfer of a
toxin must be in compliance with the requirements of this part
regardless of the amount of toxins currently in its possession.
* * * * *
0
6. Section 331.9 is amended as follows:
0
a. By removing the semicolons at the ends of paragraphs (a)(1) through
(4) and ``; and'' at the end of paragraph (a)(5) and adding periods in
their place.
0
b. In paragraph (a)(6), by removing the word ``laboratory'' and adding
the words ``registered space'' in its place and by adding the words
``and the corrections documented'' at the end of the second sentence
after the words ``must be corrected''.
0
c. By adding paragraphs (a)(7), (8), and (9).
The additions read as follows:
Sec. 331.9 Responsible official.
(a) * * *
(7) Ensure that individuals are provided the contact information
for the USDA Office of Inspector General Hotline and the HHS Office of
Inspector General Hotline so that they may anonymously report any
biosafety/biocontainment or security concerns related to select agents
and toxins.
(8) Investigate to determine the reason for any failure of a
validated inactivation procedure or any failure to remove viable select
agent from material. If the responsible official is unable to determine
the cause of a deviation from a validated inactivation procedure or a
viable select agent removal method; or receives any report of any
inactivation failure after the movement of material to another
location, the responsible official must report immediately by telephone
or email the inactivation or viable agent removal method failure to
APHIS or CDC.
(9) Review, and revise as necessary, each of the entity's validated
inactivation procedures or viable select agent removal methods. The
review must be conducted annually or after any change in principal
investigator, change in the validated inactivation procedure or viable
select agent removal method, or failure of the validated inactivation
procedure or viable select agent removal method. The review must be
documented and training must be conducted if there are any changes to
the validated inactivation procedure, viable select agent removal
method, or viability testing protocol.
* * * * *
0
7. In Sec. 331.10, paragraph (e) is amended by adding a sentence at
the end of the paragraph to read as follows:
Sec. 331.10 Restricting access to select agents and toxins; security
risk assessments.
* * * * *
(e) * * * A responsible official must immediately notify the
responsible official of the visiting entity if the person's access to
select agents or toxins has been terminated.
* * * * *
0
8. Section 331.11 is amended as follows:
0
a. In paragraph (c)(5), by adding the word ``keycards,'' after the word
``keys,'' and by removing the word ``numbers'' and adding the word
``permissions'' in its place.
0
b. In paragraph (d)(7)(iv), by removing the word ``and''.
0
c. By adding paragraph (d)(7)(vi).
0
d. By adding a sentence at the end of paragraph (h).
The additions read as follows:
Sec. 331.11 Security.
* * * * *
(d) * * *
(7) * * *
(vi) Any loss of computer, hard drive or other data storage device
containing information that can be used to gain access to select agents
or toxins; and
* * * * *
(h) * * * Drills or exercises must be documented to include how the
drill or exercise tested and evaluated the plan, any problems that were
identified and corrective action(s) taken, and the names of registered
entity personnel participants.
0
9. Section 331.12 is amended as follows:
0
a. By revising paragraph (a).
0
b. By adding a sentence at the end of paragraph (e).
The addition and revision read as follows:
Sec. 331.12 Biocontainment.
(a) An individual or entity required to register under this part
must develop and implement a written biocontainment plan that is
commensurate with the risk of the select agent or toxin, given its
intended use.\4\ The biocontainment plan must contain sufficient
information and documentation to describe the biocontainment procedures
for the select agent or toxin, including any animals (including
arthropods) or plants intentionally or accidentally exposed to or
infected with a select agent. The current biocontainment plan must be
submitted for initial registration, renewal of registration, or when
requested. The biocontainment plan must include the following
provisions:
---------------------------------------------------------------------------
\4\ Technical assistance and guidance may be obtained by
contacting APHIS.
---------------------------------------------------------------------------
(1) The hazardous characteristics of each agent or toxin listed on
the entity's registration and the biocontainment risk associated with
laboratory procedures related to the select agent or toxin;
(2) Safeguards in place with associated work practices to protect
entity personnel, the public, and the environment from exposure to the
select agent or toxin including, but not limited to: Personal
protective equipment and other safety equipment; containment equipment
including, but not limited to, biological safety cabinets, animal
caging systems, and centrifuge safety containers; and engineering
controls and other facility safeguards;
(3) Written procedures for each validated method used for
disinfection, decontamination, or destruction, as appropriate, of all
contaminated or presumptively contaminated materials including, but not
limited to: Cultures and other materials related to the propagation of
select agents or toxins, items related to the analysis of select agents
and toxins, personal protective equipment, arthropod containment
systems, extracted plant and/or arthropod tissues, laboratory surfaces
and equipment, and effluent material; and
(4) Procedures for the handling of select agents and toxins in the
same
[[Page 6206]]
spaces with non-select agents and toxins to prevent unintentional
contamination.
* * * * *
(e) * * * Drills or exercises must be documented to include how the
drill or exercise tested and evaluated the plan, any problems that were
identified and corrective action(s) taken, and the names of registered
entity personnel participants.
0
10. Section 331.14 is amended as follows:
0
a. By adding a sentence at the end of paragraph (a).
0
b. By adding a sentence at the end of paragraph (f).
The additions read as follows:
Sec. 331.14 Incident response.5
---------------------------------------------------------------------------
\5\ Nothing in this section is meant to supersede or preempt
incident response requirements imposed by other statutes or
regulations.
---------------------------------------------------------------------------
(a) * * * The current incident response plan must be submitted for
initial registration, renewal of registration, or when requested.
* * * * *
(f) * * * Drills or exercises must be documented to include how the
drill or exercise tested and evaluated the plan, any problems that were
identified and corrective action(s) taken, and the names of registered
entity personnel participants.
0
11. Section 331.15 is amended as follows:
0
a. By revising paragraph (a).
0
b. By adding paragraph (e).
The addition and revision read as follows:
Sec. 331.15 Training.
(a) An individual or entity required to register under this part
must provide information and training on biocontainment, biosafety,
security (including security awareness), and incident response to:
(1) Each individual with access approval from the Administrator or
HHS Secretary. The training must address the particular needs of the
individual, the work they will do, and the risks posed by the select
agents or toxins. The training must be accomplished prior to the
individual's entry into an area where a select agent is handled or
stored, or within 12 months of the date the individual was approved by
the Administrator or the HHS Secretary for access, whichever is
earlier.
(2) Each individual not approved for access to select agents and
toxins by the Administrator or HHS Secretary before that individual
enters areas under escort where select agents or toxins are handled or
stored (e.g., laboratories, growth chambers, animal rooms, greenhouses,
storage areas, shipping/receiving areas, production facilities, etc.).
Training for escorted personnel must be based on the risk associated
with accessing areas where select agents and toxins are used and/or
stored. The training must be accomplished prior to the individual's
entry into where select agents or toxins are handled or stored (e.g.,
laboratories, growth chambers, animal rooms, greenhouses, storage
areas, shipping/receiving areas, production facilities, etc.).
* * * * *
(e) The responsible official must ensure and document that
individuals are provided the contact information of the USDA Office of
Inspector General Hotline and the HHS Office of Inspector General
Hotline so that they may anonymously report any safety or security
concerns related to select agents and toxins.
0
12. In Sec. 331.16, paragraph (b) introductory text is revised to read
as follows:
Sec. 331.16 Transfers.
* * * * *
(b) A transfer may be authorized if:
* * * * *
0
13. Section 331.17 is amended as follows:
0
a. In paragraph (a)(1)(iii), by adding the words ``or other storage
container'' after the word ``freezer''.
0
b. By revising paragraph (a)(1)(v).
0
c. In paragraph (a)(3)(v), by adding the words ``or other storage
container'' after the word ``freezer''.
0
d. By removing the word ``and'' at the end of paragraph (a)(6) and
removing the period at the end of paragraph (a)(7) and adding ``; and''
in its place.
0
e. By adding paragraph (a)(8).
0
f. By revising paragraphs (b) and (c).
The addition and revisions read as follows:
Sec. 331.17 Records.
(a) * * *
(1) * * *
(v) The select agent used, purpose of use, and, when applicable,
final disposition;
* * * * *
(8) For select agents or material containing select agents or
regulated nucleic acids that can produce infectious forms of any select
agent virus that have been subjected to a validated inactivation
procedure or a procedure for removal of viable select agent:
(i) A written description of the validated inactivation procedure
or viable select agent removal method used, including validation data;
(ii) A written description of the viability testing protocol used;
(iii) A written description of the investigation conducted by the
entity responsible official involving an inactivation or viable select
agent removal failure and the corrective actions taken;
(iv) The name of each individual performing the validated
inactivation or viable select agent removal method;
(v) The date(s) the validated inactivation or viable select agent
removal method was completed;
(vi) The location where the validated inactivation or viable select
agent removal method was performed; and
(vii) A certificate, signed by the principal investigator, that
includes the date of inactivation or viable select agent removal, the
validated inactivation or viable select agent removal method used, and
the name of the principal investigator. A copy of the certificate must
accompany any transfer of inactivated or select agent removed material.
(b) The individual or entity must implement a system to ensure that
all records and databases created under this part are accurate and
legible, have controlled access, and that their authenticity may be
verified.
(c) The individual or entity must promptly produce upon request any
information that is related to the requirements of this part but is not
otherwise contained in a record required to be kept by this section.
The location of such information may include, but is not limited to,
biocontainment certifications, laboratory notebooks, institutional
biosafety and/or animal use committee minutes and approved protocols,
and records associated with occupational health and suitability
programs. All records created under this part must be maintained for 3
years.
Title 9--Animals and Animal Products
PART 121--POSSESSION, USE, AND TRANSFER OF SELECT AGENTS AND TOXINS
0
14. The authority citation for part 121 continues to read as follows:
Authority: 7 U.S.C. 8401; 7 CFR 2.22, 2.80, and 371.4.
0
15. Section 121.1 is amended by adding, in alphabetical order,
definitions of principal investigator, validated inactivation
procedure, and viability testing protocol to read as follows:
Sec. 121.1 Definitions.
* * * * *
[[Page 6207]]
Principal investigator. The one individual who is designated by the
entity to direct a project or program and who is responsible to the
entity for the scientific and technical direction of that project or
program.
* * * * *
Validated inactivation procedure. A procedure, whose efficacy is
confirmed by data generated from a viability testing protocol, to
render a select agent non-viable but allows the select agent to retain
characteristics of interest for future use; or to render any nucleic
acids that can produce infectious forms of any select agent virus non-
infectious for future use.
* * * * *
Viability testing protocol. A protocol to confirm the validated
inactivation procedure by demonstrating the material is free of all
viable select agent.
* * * * *
0
16. Section 121.3 is amended as follows:
0
a. By revising paragraph (d)(2).
0
b. By redesignating paragraph (d)(3) as paragraph (d)(4).
0
c. By adding a new paragraph (d)(3).
0
d. By revising newly redesignated paragraph (d)(4).
0
e. By adding paragraphs (d)(5) through (9) and (e)(3).
The additions and revisions read as follows:
Sec. 121.3 VS select agents and toxins.
* * * * *
(d) * * *
(2) Nonviable VS select agents or nontoxic VS toxins.\3\
---------------------------------------------------------------------------
\3\ However, the importation and interstate movement of these
nonviable select agents may be subject to the permit requirements
under part 122 of this subchapter.
---------------------------------------------------------------------------
(3) A select agent or toxin that has been subjected to
decontamination or a destruction procedure when intended for waste
disposal.
(4) A select agent or regulated nucleic acids that can produce
infectious forms of any select agent virus that has been subjected to a
validated inactivation procedure that is confirmed through a viability
testing protocol. Surrogate strains that are known to possess
equivalent properties with respect to inactivation can be used to
validate an inactivation procedure; however, if there are known strain-
to-strain variations in the resistance of a select agent to an
inactivation procedure, then an inactivation procedure validated on a
lesser resistant strain must also be validated on the more resistant
strains.
(5) Material containing a select agent that is subjected to a
procedure that removes all viable select agent cells, spores, or virus
particles if the material is subjected to a viability testing protocol
to ensure that the removal method has rendered the material free of all
viable select agent.
(6) A select agent or regulated nucleic acids that can produce
infectious forms of any select agent virus not subjected to a validated
inactivation procedure or material containing a select agent not
subjected to a procedure that removes all viable select agent cells,
spores, or virus particles if the material is determined by the
Administrator to be effectively inactivated or effectively removed. To
apply for a determination an individual or entity must submit a written
request and supporting scientific information to APHIS. A written
decision granting or denying the request will be issued.
(7) A VS select toxin identified in an original food sample or
clinical sample.
(8) Waste generated during the delivery of patient care by health
care professionals from a patient diagnosed with an illness or
condition associated with a select agent, where that waste is
decontaminated or transferred for destruction by complying with State
and Federal regulations within 7 calendar days of the conclusion of
patient care.
(9) Any low pathogenic strains of avian influenza virus, avian
paramyxovirus serotype-1 (APMV-1) viruses which do not meet the
criteria for Newcastle disease virus,\4\ including those identified as
pigeon paramyxovirus-12 \5\ isolated from a non-poultry species, all
subspecies Mycoplasma capricolum except subspecies capripneumoniae
(contagious caprine pleuropneumonia), and all subspecies Mycoplasma
mycoides except subspecies mycoides small colony (Mmm SC) (contagious
bovine pleuropneumonia), provided that the individual or entity can
identify that the agent is within the exclusion category.
---------------------------------------------------------------------------
\4\ An APMV-1 virus isolated from poultry which has an
intracerebral pathogenicity index in day[hyphen]old chicks (Gallus
gallus) of 0.7 or greater or has an amino acid sequence at the
fusion (F) protein cleavage site that is consistent with virulent
strains of Newcastle disease virus. A failure to detect a cleavage
site that is consistent with virulent strains does not confirm the
absence of a virulent virus.
\5\ Pigeon paramyxovirus (PPMV-1) is a species-adapted APMV-1
virus which is endemic in pigeons and doves in the United States and
can be identified through monoclonal antibody testing and
demonstration of their characteristic amino acid signature at the
fusion gene cleavage site.
---------------------------------------------------------------------------
(e) * * *
(3) An individual or entity may make a written request to the
Administrator for reconsideration of a decision denying an application
for the exclusion of an attenuated strain of a select agent or a select
toxin modified to be less potent or toxic. The written request for
reconsideration must state the facts and reasoning upon which the
individual or entity relies to show the decision was incorrect. The
Administrator will grant or deny the request for reconsideration as
promptly as circumstances allow and will state, in writing, the reasons
for the decision.
* * * * *
0
17. Section 121.4 is amended as follows:
0
a. In paragraph (c)(1), by redesignating footnote 4 as footnote 6.
0
b. In paragraph (c)(2) introductory text, by removing the word
``functional'' and adding in its place the word ``toxic''.
0
c. By revising paragraph (d)(2).
0
d. By redesignating paragraph (d)(3) as paragraph (d)(9).
0
e. By adding paragraphs (d)(3) through (8) and (e)(3).
The additions and revision read as follows:
Sec. 121.4 Overlap select agents and toxins.
* * * * *
(d) * * *
(2) Nonviable overlap select agents or nontoxic overlap toxins.\7\
---------------------------------------------------------------------------
\7\ However, the importation and interstate movement of these
nonviable overlap select agents may be subject to the permit
requirements under part 122 of this subchapter.
---------------------------------------------------------------------------
(3) A select agent or toxin that has been subjected to
decontamination or a destruction procedure when intended for waste
disposal.
(4) A select agent or regulated nucleic acids that can produce
infectious forms of any select agent virus that has been subjected to a
validated inactivation procedure that is confirmed through a viability
testing protocol. Surrogate strains that are known to possess
equivalent properties with respect to inactivation can be used to
validate an inactivation procedure; however, if there are known strain-
to-strain variations in the resistance of a select agent to an
inactivation procedure, then an inactivation procedure validated on a
lesser resistant strain must also be validated on the more resistant
strains.
(5) Material containing a select agent that is subjected to a
procedure that removes all viable select agent cells, spores, or virus
particles if the material is subjected to a viability testing protocol
to ensure that the removal method has rendered the material free of all
viable select agent.
(6) A select agent or regulated nucleic acids that can produce
infectious forms of any select agent virus not subjected
[[Page 6208]]
to a validated inactivation procedure or material containing a select
agent not subjected to a procedure that removes all viable select agent
cells, spores, or virus particles if the material is determined by the
Administrator or HHS Secretary to be effectively inactivated or
effectively removed. To apply for a determination an individual or
entity must submit a written request and supporting scientific
information to APHIS or CDC. A written decision granting or denying the
request will be issued.
(7) An overlap select toxin identified in an original food sample
or clinical sample.
(8) Waste generated during the delivery of patient care by health
care professionals from a patient diagnosed with an illness or
condition associated with a select agent, where that waste is
decontaminated or transferred for destruction by complying with State
and Federal regulations within 7 calendar days of the conclusion of
patient care.
* * * * *
(e) * * *
(3) An individual or entity may make a written request to the
Administrator or HHS Secretary for reconsideration of a decision
denying an application for the exclusion of an attenuated strain of a
select agent or a select toxin modified to be less potent or toxic. The
written request for reconsideration must state the facts and reasoning
upon which the individual or entity relies to show the decision was
incorrect. The Administrator or HHS Secretary will grant or deny the
request for reconsideration as promptly as circumstances allow and will
state, in writing, the reasons for the decision.
* * * * *
0
18. In Sec. 121.5, paragraph (a) is revised as follows:
Sec. 121.5 Exemptions for VS select agents and toxins.
(a) Diagnostic laboratories and other entities that possess, use,
or transfer a VS select agent or toxin that is contained in a specimen
presented for diagnosis or verification will be exempt from the
requirements of this part for such agent or toxin contained in the
specimen, provided that:
(1) Unless directed otherwise by the Administrator, within 7
calendar days after identification of the select agent or toxin, the
select agent or toxin is transferred in accordance with Sec. 121.16 or
destroyed on-site by a recognized sterilization or inactivation
process;
(2) The agent or toxin is secured against theft, loss, or release
during the period between identification of the agent or toxin and
transfer or destruction of such agent or toxin, and any theft, loss, or
release of such agent or toxin is reported;
(3) Unless otherwise directed by the Administrator, the clinical or
diagnostic specimens collected from a patient infected with a select
agent are transferred in accordance with Sec. 121.16 or destroyed on-
site by a recognized sterilization or inactivation process within 7
calendar days after delivery of patient care by heath care
professionals has concluded; and
(4) The identification of the agent or toxin is reported to APHIS
or CDC, the specimen provider, and to other appropriate authorities
when required by Federal, State, or local law by telephone, facsimile,
or email. This report must be followed by submission of APHIS/CDC Form
4 to APHIS or CDC within 7 calendar days after identification.
* * * * *
0
19. Section 121.6 is amended as follows:
0
a. By revising paragraph (a)(1).
0
b. In paragraph (a)(2), by removing the word ``and'' at the end of the
paragraph.
0
c. By redesignating paragraph (a)(3) as paragraph (a)(4).
0
d. By adding new paragraph (a)(3).
0
e. By revising newly redesignated paragraph (a)(4).
The addition and revisions read as follows:
Sec. 121.6 Exemptions for overlap select agents and toxins.
(a) * * *
(1) Unless directed otherwise by the Administrator, within 7
calendar days after identification of the select agent or toxin, the
select agent or toxin is transferred in accordance with Sec. 121.16 or
destroyed on-site by a recognized sterilization or inactivation
process;
* * * * *
(3) Unless otherwise directed by the Administrator or HHS
Secretary, the clinical or diagnostic specimens collected from a
patient infected with a select agent are transferred in accordance with
Sec. 121.16 or destroyed on-site by a recognized sterilization or
inactivation process within 7 calendar days after delivery of patient
care by heath care professionals has concluded; and
(4) The identification of the agent or toxin is reported to APHIS
or CDC, the specimen provider, and to other appropriate authorities
when required by Federal, State, or local law by telephone, facsimile,
or email. This report must be followed by submission of APHIS/CDC Form
4 to APHIS or CDC within 7 calendar days after identification.
* * * * *
0
20. Section 121.7 is amended as follows:
0
a. By redesignating paragraphs (b) through (k) as paragraphs (c)
through (l), respectively.
0
b. By adding a new paragraph (b).
0
c. In newly redesignated paragraph (d)(3) introductory text, by
redesignating footnote 6 as footnote 8.
0
d. In newly redesignated paragraph (i)(1), by redesignating footnote 7
as footnote 9.
The addition reads as follows:
Sec. 121.7 Registration and related security risk assessments.
* * * * *
(b) As a condition of registration, each entity is required to be
in compliance with the requirements of this part for select agents and
toxins listed on the registration regardless of whether the entity is
in actual possession of the select agent or toxin. With regard to
toxins, the entity registered for possession, use, or transfer of a
toxin must be in compliance with the requirements of this part
regardless of the amount of toxins currently in its possession.
* * * * *
Sec. 121.8 [Amended]
0
21. In Sec. 121.8, footnote 8 is redesignated as footnote 10.
0
22. Section 121.9 is amended as follows:
0
a. By removing the semicolons at the ends of paragraphs (a)(1) through
(4) and ``; and'' at the end of paragraph (a)(5) an adding periods in
their place.
0
b. In paragraph (a)(6), by removing the word ``laboratory'' and adding
the words ``registered space'' in its place and by adding the words
``and the corrections documented'' at the end of the second sentence
after the words ``must be corrected''.
0
c. By adding paragraphs (a)(7), (8), and (9).
The additions read as follows:
Sec. 121.9 Responsible official.
(a) * * *
(7) Ensure that individuals are provided the contact information
for the USDA Office of Inspector General Hotline and the HHS Office of
Inspector General Hotline so that they may anonymously report any
biosafety/biocontainment or security concerns related to select agents
and toxins.
(8) Investigate to determine the reason for any failure of a
validated
[[Page 6209]]
inactivation procedure or any failure to remove viable select agent
from material. If the responsible official is unable to determine the
cause of a deviation from a validated inactivation procedure or a
viable select agent removal method; or receives any report of any
inactivation failure after the movement of material to another
location, the responsible official must report immediately by telephone
or email the inactivation or viable agent removal method failure to
APHIS or CDC.
(9) Review, and revise as necessary, each of the entity's validated
inactivation procedures or viable select agent removal methods. The
review must be conducted annually or after any change in principal
investigator, change in the validated inactivation procedure or viable
select agent removal method, or failure of the validated inactivation
procedure or viable select agent removal method. The review must be
documented and training must be conducted if there are any changes to
the validated inactivation procedure, viable select agent removal
method, or viability testing protocol.
* * * * *
0
23. In Sec. 121.10, paragraph (e) is amended by adding a sentence at
the end of the paragraph to read as follows:
Sec. 121.10 Restricting access to select agents and toxins; security
risk assessments.
* * * * *
(e) * * * A responsible official must immediately notify the
responsible official of the visited entity if the person's access to
select agents and toxins has been terminated.
* * * * *
0
24. Section 121.11 is amended as follows:
0
a. In paragraph (c)(5), by adding the word ``keycards,'' after the word
``keys,'' and by removing the word ``numbers'' and adding the word
``permissions'' in its place.
0
b. In paragraph (d)(7)(iv), by removing the word ``and''.
0
c. By adding paragraph (d)(7)(vi).
0
d. By adding a sentence at the end of paragraph (h).
The additions read as follows:
Sec. 121.11 Security.
* * * * *
(d) * * *
(7) * * *
(vi) Any loss of computer, hard drive or other data storage device
containing information that could be used to gain access to select
agents or toxins; and
* * * * *
(h) * * * Drills or exercises must be documented to include how the
drill or exercise tested and evaluated the plan, any problems that were
identified and corrective action(s) taken, and the names of registered
entity personnel participants.
0
25. Section 121.12 is amended as follows:
0
a. By revising paragraph (a).
0
b. By removing paragraph (c)(2).
0
c. By redesignating paragraph (c)(3) as paragraph (c)(2), and in newly
redesignated paragraph (c)(2), removing the words ``NIH Guidelines for
Research Involving Recombinant DNA Molecules'' and adding in their
place the words ``NIH Guidelines for Research Involving Recombinant or
Synthetic Nucleic Acid Molecules''.
0
d. By adding a sentence at the end of paragraph (e).
The addition and revision read as follows:
Sec. 121.12 Biosafety.
(a) An individual or entity required to register under this part
must develop and implement a written biosafety plan that is
commensurate with the risk of the select agent or toxin, given its
intended use.\11\ The biosafety plan must contain sufficient
information and documentation to describe the biosafety and containment
procedures for the select agent or toxin, including any animals
(including arthropods) or plants intentionally or accidentally exposed
to or infected with a select agent. The current biosafety plan must be
submitted for initial registration, renewal of registration, or when
requested. The biosafety plan must include the following provisions:
---------------------------------------------------------------------------
\11\ Technical assistance and guidance may be obtained by
contacting APHIS.
---------------------------------------------------------------------------
(1) The hazardous characteristics of each agent or toxin listed on
the entity's registration and the biosafety risk associated with
laboratory procedures related to the select agent or toxin;
(2) Safeguards in place with associated work practices to protect
entity personnel, the public, and the environment from exposure to the
select agent or toxin including, but not limited to: Personal
protective equipment and other safety equipment; containment equipment
including, but not limited to, biological safety cabinets, animal
caging systems, and centrifuge safety containers; and engineering
controls and other facility safeguards;
(3) Written procedures for each validated method used for
disinfection, decontamination, or destruction, as appropriate, of all
contaminated or presumptively contaminated materials including, but not
limited to: Cultures and other materials related to the propagation of
select agents or toxins, items related to the analysis of select agents
and toxins, personal protective equipment, animal caging systems and
bedding (if applicable), animal carcasses or extracted tissues and
fluids (if applicable), laboratory surfaces and equipment, and effluent
material; and
(4) Procedures for the handling of select agents and toxins in the
same spaces with non-select agents and toxins to prevent unintentional
contamination.
* * * * *
(e) * * * Drills or exercises must be documented to include how the
drill or exercise tested and evaluated the plan, any problems that were
identified and corrective action(s) taken, and the names of registered
entity personnel participants.
0
26. Section 121.14 is amended as follows:
0
a. In the section heading, by redesignating footnote 10 as footnote 12.
0
b. In paragraph (a), by redesignating footnote 11 as footnote 13, and
by adding a sentence at the end of the paragraph.
0
c. In paragraph (f), by adding a sentence at the end of the paragraph.
The additions read as follows:
Sec. 121.14 Incident response.\12\
---------------------------------------------------------------------------
\12\ Nothing in this section is meant to supersede or preempt
incident response requirements imposed by other statutes or
regulations.
---------------------------------------------------------------------------
(a) * * * The current incident response plan must be submitted for
initial registration, renewal of registration, or when requested.
* * * * *
(f) * * * Drills or exercises must be documented to include how the
drill or exercise tested and evaluated the plan, any problems that were
identified and corrective action(s) taken, and the names of registered
entity personnel participants.
0
27. Section 121.15 is amended as follows:
0
a. By revising paragraph (a).
0
e. By adding paragraph (e).
The addition and revision read as follows:
Sec. 121.15 Training.
(a) An individual or entity required to register under this part
must provide information and training on biocontainment, biosafety,
security (including security awareness), and incident response to:
(1) Each individual with access approval from the Administrator or
HHS Secretary. The training must address the particular needs of the
individual, the
[[Page 6210]]
work they will do, and the risks posed by the select agents or toxins.
The training must be accomplished prior to the individual's entry into
an area where a select agent is handled or stored, or within 12 months
of the date the individual was approved by the Administrator or the HHS
Secretary for access, whichever is earlier.
(2) Each individual not approved for access to select agents and
toxins by the Administrator or HHS Secretary before that individual
enters areas under escort where select agents or toxins are handled or
stored (e.g., laboratories, growth chambers, animal rooms, greenhouses,
storage areas, shipping/receiving areas, production facilities, etc.).
Training for escorted personnel must be based on the risk associated
with accessing areas where select agents and toxins are used and/or
stored. The training must be accomplished prior to the individual's
entry into where select agents or toxins are handled or stored (e.g.,
laboratories, growth chambers, animal rooms, greenhouses, storage
areas, shipping/receiving areas, production facilities, etc.).
* * * * *
(e) The responsible official must ensure and document that
individuals are provided the contact information of the USDA Office of
Inspector General Hotline and the HHS Office of Inspector General
Hotline so that they may anonymously report any safety or security
concerns related to select agents and toxins.
0
28. Section Sec. 121.16 is amended as follows:
0
a. In paragraph (a), by redesignating footnote 12 as footnote 14.
0
b. By revising paragraph (b) introductory text.
0
c. By adding paragraph (l).
The addition and revision read as follows:
Sec. 121.16 Transfers.
* * * * *
(b) A transfer may be authorized if:
* * * * *
(l) Transfer the amounts only after the transferor uses due
diligence and documents that the recipient has a legitimate need (e.g.,
prophylactic, protective, bona fide research, or other peaceful
purpose) to handle or use such toxins. Information to be documented
includes, but is not limited, to the recipient information, toxin and
amount transferred, and declaration that the recipient has legitimate
purpose to store and use such toxins.
0
29. Section 121.17 is amended as follows:
0
a. In paragraph (a)(1)(iii), by adding the words ``or other storage
container'' after the word ``freezer''.
0
b. By revising paragraph (a)(1)(v).
0
c. In paragraph (a)(3)(v), by adding the words ``or other storage
container'' after the word ``freezer''.
0
d. By removing the word ``and'' at the end of paragraph (a)(6) and
removing the period at the end of paragraph (a)(7) and adding the word
``; and'' in its place.
0
e. By adding paragraph (a)(8).
0
f. By revising paragraphs (b) and (c).
The addition and revisions read as follows:
Sec. 121.17 Records.
(a) * * *
(1) * * *
(v) The select agent used, purpose of use, and, when applicable,
final disposition;
* * * * *
(8) For select agents or material containing select agents or
regulated nucleic acids that can produce infectious forms of any select
agent virus that have been subjected to a validated inactivation
procedure or a procedure for removal of viable select agent:
(i) A written description of the validated inactivation procedure
or viable select agent removal method used, including validation data;
(ii) A written description of the viability testing protocol used;
(iii) A written description of the investigation conducted by the
entity responsible official involving an inactivation or viable select
agent removal failure and the corrective actions taken;
(iv) The name of each individual performing the validated
inactivation or viable select agent removal method;
(v) The date(s) the validated inactivation or viable select agent
removal method was completed;
(vi) The location where the validated inactivation or viable select
agent removal method was performed; and
(vii) A certificate, signed by the principal investigator, that
includes the date of inactivation or viable select agent removal, the
validated inactivation or viable select agent removal method used, and
the name of the principal investigator. A copy of the certificate must
accompany any transfer of inactivated or select agent removed material.
(b) The individual or entity must implement a system to ensure that
all records and databases created under this part are accurate and
legible, have controlled access, and that their authenticity may be
verified.
(c) The individual or entity must promptly produce upon request any
information that is related to the requirements of this part but is not
otherwise contained in a record required to be kept by this section.
The location of such information may include, but is not limited to,
biocontainment certifications, laboratory notebooks, institutional
biosafety and/or animal use committee minutes and approved protocols,
and records associated with occupational health and suitability
programs. All records created under this part must be maintained for 3
years.
Done in Washington, DC, this 10th day of January 2017.
Elvis S. Cordova,
Acting Under Secretary for Marketing and Regulatory Programs.
[FR Doc. 2017-00857 Filed 1-18-17; 8:45 am]
BILLING CODE 3410-34-P